The tumor suppressor p53 triggers cell-cycle arrest and apoptosis but about 50% of human tumors have mutations in p53 which makes them resistant to apoptosis. Vladimir Bykov and colleagues from Karolinska Institutet, Stockholm, Sweden hypothesized that restoring p53 in tumor cells could trigger massive apoptosis and eliminate the tumor. In March Nature Medicine, they show that a small molecule, called PRIMA-1, can restore the tumor suppressor function of p53 and have anti-tumor effects.

Bykov et al. screened low-molecular-weight compounds and identified a molecule (named PRIMA-1) capable of inducing apoptosis in human tumor cells through restoration of the transcriptional transactivation function to mutant p53. PRIMA-1 restored sequence-specific DNA binding and the active conformation to mutant p53 proteins in vitro and in living cells. In addition, in vivo studies in mice revealed an anti-tumor effect of PRIMA-1 with no apparent toxicity (Nat Med 2002, 8:282-288).


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